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Acute mercury poisoning (acrodynia) mimickingpheochromocytoma in an adolescent
252
Henningsson el al.
The Journal of Pediatrics February 1993
Acute mercury poisoning (acrodynia) mimicking p h e o c h r o m o c y t o m a in an a d o l e s c e n t C. Henningsson, MD, PhD, S. Hoffmann, MD, L. McGonigle, MD, FRCP(C), and J. S. D. Winter, MD, FRCP(C) From the Department of Pediatrlcs, University of Alberta, Edmonton, Alberta, Canada
A 14-year-old boy was seen because of Irritability, Insomnia, lethargy, and profuse sweating, together with hypertension (blood pressure: 160/120 mm Hg), tachycardla, and a diffuse erythematous rash with desquamatlon of the palms and soles. Initial biochemical Investigation suggested a diagnosis of pheochromocytoma, but subsequently a history of exposure to mercury vapor was obtained. This case emphaslzes the cllnlcal and blochemical similarities between mercury poisoning (acrodynla) and pheochromocytoma. (J PEDIATR 1993;122:252-3)
In the absence of a family history of multiple endocrine neoplasia (types 2 and 3), neurofibromatosis, or yon Hippel-Lindau disease, making the diagnosis of pheochromocytoma can be difficult. The tumor is particularly rare in the pediatric age group. I Classic manifestations of pheochromocytoma include paroxysmal headache, pallor, sweating, palpitations, and anxiety, in association with significant hypertension. Biochemical confirmation depends on the demonstration of increased levels of plasma and urinary catecholamines; diagnostic confidence can be enhanced by the demonstration that catecholamine levels are not suppressed by orally administered clonidine. 2 Anatomic localization can then be accomplished with ultrasonography, computed tomography, and scanning after administration of m-iodobenzylguanidine labeled with iodine 131. The purpose of this report is to demonstrate that acute mercury poisoning (acrodynia) can mimic the clinical and biochemical manifestations of pheochromocytoma, and should be considered and excluded during the investigation of suspected cases.
CASE R E P O R T A 14-year-old boy had been seen by his physician 3 weeks previously with complaints of back pain and was discovered to have tachycardia and a blood pressure of 160/120 mm llg. Laboratory
Submitted for publication June 23, 1992; accepted Sept. 1!, 1992. Reprint requests: J. S. D. Winter, MD, FRCP(C), Professor, Department of Pediatrics, Section of Endocrinology and Metabolism, 671 lleritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Copyright 9 1993 by Mosby-Ycar Book, Inc. 0022-3476/93/$1.00 + .10 9/22/42499
values included the following: hemoglobin, 18.9 gm/L; calcium, 2.84 mmol/L, uric acid, 489 mmol/L; and albumin, 55 gm/L (all evidence of apparent hemoconcentration). Although the patient's back pain resolved, there was no blood pressure response to therapy with nifedipine and phenoxybenzamine. Subsequently a generalized, pruritic erythematous rash developed, with desquamation on the palms and soles. The patient began to have paroxysmal episodes of sweating accompanied, by chills and tremor, to a degree that required a change of bed linen every 2 hours, lie became increasingly irritable, complained of insomnia, and lost 4 kg weight. Initially he had anorexia, but subsequently his appetite became voracious, requiring extra meals through the night, tte also complained of decreased energy and episodic sensations of heat and cold. Exposure to drugs and toxins was denied, except for occasional use of alcohol. IIe had a history of penicillin allergy. There was no family history of hypertension, pheochromocytoma, or multiple endocrine neoplasia syndromes. On examination the patient was irritable but in no immediate distress. His blood pressure was 140/100 mm ttg while he was supine, 130/60 while sitting, and 90/50 while standing; he was still taking the antihypertensive medications, tie was afebrile. Ills height was at the 50th percentile and his weight at the 25th. There was a generalized, blanching maculopapular rash, confluent over the trunk, with desquamation on the palms and soles. His thyroid gland was normal and there was no exophthalmos. His cardiovascular and neurologie examinations were otherwise normal. His abdomen was soft, with no abnormal masses, no tenderness, and no bruits. Laboratory investigation showed normal thyroid function. A diagnosis of pheochromocytoma appeared to be confirmed by demonstration of increased basal plasma and urinary catecholamines, with no evidence of suppression by elonidine, 300 ~tg by mouth (Table I). tlowever, abdominal computed tomographic scans and radiographs of the chest failed to show a tumor, and two separate m-[13q]iodobenzylguanidine scans showed normal adrenal glands and no evidence for extraadrenal pheochromocytoma.
The Journal of Pediatrics Volume 122, Number 2
Henningsson et al.
253
T a b l e I. Catecholamine values in acute mercury poisoning Clonldlne lest
Plasma (nmol/L) Norepinephrine Epinephrine Dopamine Urine (nmol/24 hr) Metanephrine Catecholamines
Basal value
- 4 5 mln
0 mln
+120 mln
Normal range
13.80 3.61 3.29
11.16 1.01 0.37
9.39 1.01 0.82
15.68 1.63 2.01
0.66-3.56 <0.34 <0.54
0.60 5.05
<0.6 0-1.5
Clonidine suppression test: Clonidine, 300 ~g, was given orally at time zero; plasma catecholamioes ,~ere measured at -30, -15, 0, +120, and +180 minutes. Normal response is a 50% fall in catecholamine levels. The patient's clinical condition rapidly deteriorated, and he began to have hallucinations. At the third review of the history, in response to direct questions about mercury exposure, he admitted to playing with elemental mercury, with extensive skin contact, and to having been exposed to mercury vapor after the metal had been poured into a portable electric coil heater. Use of the heater continued during visits home from the hospital. Blood and urinary mercury levels were elevated in the boy and his parents (Table II). Because of penicillin allergy, the boy was treated with dimercaprol; although mercury levels and blood pressure returned to normal during the next 4 months, and his symptoms disappeared, he was subsequently readmitted to the hospital with seizures. The mother also had symptoms (tremors, weakness, rash, memory loss, sweating, and palpitations) but no hypertension; the father had mild memory loss. Both parents were treated with penicillamine until their mercury levels returned to normal. Their house had to be stripped and cleaned to prevent further mercury exposure. DISCUSSION Since an association with mercury exposure was demonstrated, 3-5 acrodynia has become a rare disease, largely unknown to physicians. In the past, many authors pointed to the clinical similarities between acrodynia and pheochromocytoma; although early catecholamine assays were of dubious validity, at least two authors reported increased epinephrine and norepinephrine excretion in acrodynia. 6 Cheek et al. 7 showed that inorganic mercury by injection can markedly increase sympathetic activity and epinephrine levels in rats, and would therefore be expected to mimic the signs and symptoms of pheochromocytoma. In our patient we were able to document elevated catecholamine levels and to demonstrate that they were not suppressed by clonidine, findings that would commonly be considered diagnostic of pheochromocytoma. Only our inability to localize a tumor delayed his planned surgery, and eventually led to the correct diagnosis of mercury poisoning by the more mundane process of careful history taking. Acrodynia in an adolescent is virtually unheard of but should not be entirely unsuspected, given the current recreational nature of mercury exposure. Indeed, during the past year we
T a b l e II. Mercury levels in acute mercury poisoning
Patient Mother Father Normal range
Blood (nmol/L)
Urine (nmol/t)
1 I0 50 50 <25
400 920 480 <50
Serum and urine mercuryconcentrations of the patient and the parents (the only other residents of the household).
have seen three other children in this hospital who had significant exposure to elemental mercury. It is ironic, with the rarity of pheochromocytoma in children, that all current textbooks on pediatrics or endocrinology devote considerable space to this tumor, whereas few even mention acrodynia. We believe that mercury poisoning should be considered initially in any child with signs of sweating, behavioral change, skin rash, and hypertension, and that pheochromocytoma might be considered in the differential diagnosis. REFERENCES 1. Beard CMI Shaps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proo 1983;58:802-4. 2. Manneli M, DeFeo b,lL, Pupilli C, et al. Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma. J Endocrinol Invest 1987; 10:377-82. 3. Zahorsky J. Three cases of erythroedema (acrodynia) in infants. Med Clin North Am 1922;6:97-105. 4. Fanconi G, Schenker P. Uberempfindlichkeitstreaktionen auf Quecksilbermedication im kindesalter mit besonderer beruchsichtigung der calomelkrenkheit, ttelv Paediatr Acta 1947;2(suppl 4):3-46. 5. Warkany J, Hubbard DM. Mercury in the urine of children with acrodynia. Lancet 1948;1:829-30. 6. Farquhar ttG. Mercurial poisoning in early childhood. Lancet 1953;2:1186-7. 7. Cheek DB, Bandy RK, Johnson LR. The effect of mercurous chloride (calomel) and epinephrine (sympathetic stimulation) on rats: the importance of the findings to mechanisms in infantile acrodynia (pink disease). Pediatrics 1959;23:302-13.
Henningsson el al.
The Journal of Pediatrics February 1993
Acute mercury poisoning (acrodynia) mimicking p h e o c h r o m o c y t o m a in an a d o l e s c e n t C. Henningsson, MD, PhD, S. Hoffmann, MD, L. McGonigle, MD, FRCP(C), and J. S. D. Winter, MD, FRCP(C) From the Department of Pediatrlcs, University of Alberta, Edmonton, Alberta, Canada
A 14-year-old boy was seen because of Irritability, Insomnia, lethargy, and profuse sweating, together with hypertension (blood pressure: 160/120 mm Hg), tachycardla, and a diffuse erythematous rash with desquamatlon of the palms and soles. Initial biochemical Investigation suggested a diagnosis of pheochromocytoma, but subsequently a history of exposure to mercury vapor was obtained. This case emphaslzes the cllnlcal and blochemical similarities between mercury poisoning (acrodynla) and pheochromocytoma. (J PEDIATR 1993;122:252-3)
In the absence of a family history of multiple endocrine neoplasia (types 2 and 3), neurofibromatosis, or yon Hippel-Lindau disease, making the diagnosis of pheochromocytoma can be difficult. The tumor is particularly rare in the pediatric age group. I Classic manifestations of pheochromocytoma include paroxysmal headache, pallor, sweating, palpitations, and anxiety, in association with significant hypertension. Biochemical confirmation depends on the demonstration of increased levels of plasma and urinary catecholamines; diagnostic confidence can be enhanced by the demonstration that catecholamine levels are not suppressed by orally administered clonidine. 2 Anatomic localization can then be accomplished with ultrasonography, computed tomography, and scanning after administration of m-iodobenzylguanidine labeled with iodine 131. The purpose of this report is to demonstrate that acute mercury poisoning (acrodynia) can mimic the clinical and biochemical manifestations of pheochromocytoma, and should be considered and excluded during the investigation of suspected cases.
CASE R E P O R T A 14-year-old boy had been seen by his physician 3 weeks previously with complaints of back pain and was discovered to have tachycardia and a blood pressure of 160/120 mm llg. Laboratory
Submitted for publication June 23, 1992; accepted Sept. 1!, 1992. Reprint requests: J. S. D. Winter, MD, FRCP(C), Professor, Department of Pediatrics, Section of Endocrinology and Metabolism, 671 lleritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Copyright 9 1993 by Mosby-Ycar Book, Inc. 0022-3476/93/$1.00 + .10 9/22/42499
values included the following: hemoglobin, 18.9 gm/L; calcium, 2.84 mmol/L, uric acid, 489 mmol/L; and albumin, 55 gm/L (all evidence of apparent hemoconcentration). Although the patient's back pain resolved, there was no blood pressure response to therapy with nifedipine and phenoxybenzamine. Subsequently a generalized, pruritic erythematous rash developed, with desquamation on the palms and soles. The patient began to have paroxysmal episodes of sweating accompanied, by chills and tremor, to a degree that required a change of bed linen every 2 hours, lie became increasingly irritable, complained of insomnia, and lost 4 kg weight. Initially he had anorexia, but subsequently his appetite became voracious, requiring extra meals through the night, tte also complained of decreased energy and episodic sensations of heat and cold. Exposure to drugs and toxins was denied, except for occasional use of alcohol. IIe had a history of penicillin allergy. There was no family history of hypertension, pheochromocytoma, or multiple endocrine neoplasia syndromes. On examination the patient was irritable but in no immediate distress. His blood pressure was 140/100 mm ttg while he was supine, 130/60 while sitting, and 90/50 while standing; he was still taking the antihypertensive medications, tie was afebrile. Ills height was at the 50th percentile and his weight at the 25th. There was a generalized, blanching maculopapular rash, confluent over the trunk, with desquamation on the palms and soles. His thyroid gland was normal and there was no exophthalmos. His cardiovascular and neurologie examinations were otherwise normal. His abdomen was soft, with no abnormal masses, no tenderness, and no bruits. Laboratory investigation showed normal thyroid function. A diagnosis of pheochromocytoma appeared to be confirmed by demonstration of increased basal plasma and urinary catecholamines, with no evidence of suppression by elonidine, 300 ~tg by mouth (Table I). tlowever, abdominal computed tomographic scans and radiographs of the chest failed to show a tumor, and two separate m-[13q]iodobenzylguanidine scans showed normal adrenal glands and no evidence for extraadrenal pheochromocytoma.
The Journal of Pediatrics Volume 122, Number 2
Henningsson et al.
253
T a b l e I. Catecholamine values in acute mercury poisoning Clonldlne lest
Plasma (nmol/L) Norepinephrine Epinephrine Dopamine Urine (nmol/24 hr) Metanephrine Catecholamines
Basal value
- 4 5 mln
0 mln
+120 mln
Normal range
13.80 3.61 3.29
11.16 1.01 0.37
9.39 1.01 0.82
15.68 1.63 2.01
0.66-3.56 <0.34 <0.54
0.60 5.05
<0.6 0-1.5
Clonidine suppression test: Clonidine, 300 ~g, was given orally at time zero; plasma catecholamioes ,~ere measured at -30, -15, 0, +120, and +180 minutes. Normal response is a 50% fall in catecholamine levels. The patient's clinical condition rapidly deteriorated, and he began to have hallucinations. At the third review of the history, in response to direct questions about mercury exposure, he admitted to playing with elemental mercury, with extensive skin contact, and to having been exposed to mercury vapor after the metal had been poured into a portable electric coil heater. Use of the heater continued during visits home from the hospital. Blood and urinary mercury levels were elevated in the boy and his parents (Table II). Because of penicillin allergy, the boy was treated with dimercaprol; although mercury levels and blood pressure returned to normal during the next 4 months, and his symptoms disappeared, he was subsequently readmitted to the hospital with seizures. The mother also had symptoms (tremors, weakness, rash, memory loss, sweating, and palpitations) but no hypertension; the father had mild memory loss. Both parents were treated with penicillamine until their mercury levels returned to normal. Their house had to be stripped and cleaned to prevent further mercury exposure. DISCUSSION Since an association with mercury exposure was demonstrated, 3-5 acrodynia has become a rare disease, largely unknown to physicians. In the past, many authors pointed to the clinical similarities between acrodynia and pheochromocytoma; although early catecholamine assays were of dubious validity, at least two authors reported increased epinephrine and norepinephrine excretion in acrodynia. 6 Cheek et al. 7 showed that inorganic mercury by injection can markedly increase sympathetic activity and epinephrine levels in rats, and would therefore be expected to mimic the signs and symptoms of pheochromocytoma. In our patient we were able to document elevated catecholamine levels and to demonstrate that they were not suppressed by clonidine, findings that would commonly be considered diagnostic of pheochromocytoma. Only our inability to localize a tumor delayed his planned surgery, and eventually led to the correct diagnosis of mercury poisoning by the more mundane process of careful history taking. Acrodynia in an adolescent is virtually unheard of but should not be entirely unsuspected, given the current recreational nature of mercury exposure. Indeed, during the past year we
T a b l e II. Mercury levels in acute mercury poisoning
Patient Mother Father Normal range
Blood (nmol/L)
Urine (nmol/t)
1 I0 50 50 <25
400 920 480 <50
Serum and urine mercuryconcentrations of the patient and the parents (the only other residents of the household).
have seen three other children in this hospital who had significant exposure to elemental mercury. It is ironic, with the rarity of pheochromocytoma in children, that all current textbooks on pediatrics or endocrinology devote considerable space to this tumor, whereas few even mention acrodynia. We believe that mercury poisoning should be considered initially in any child with signs of sweating, behavioral change, skin rash, and hypertension, and that pheochromocytoma might be considered in the differential diagnosis. REFERENCES 1. Beard CMI Shaps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proo 1983;58:802-4. 2. Manneli M, DeFeo b,lL, Pupilli C, et al. Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma. J Endocrinol Invest 1987; 10:377-82. 3. Zahorsky J. Three cases of erythroedema (acrodynia) in infants. Med Clin North Am 1922;6:97-105. 4. Fanconi G, Schenker P. Uberempfindlichkeitstreaktionen auf Quecksilbermedication im kindesalter mit besonderer beruchsichtigung der calomelkrenkheit, ttelv Paediatr Acta 1947;2(suppl 4):3-46. 5. Warkany J, Hubbard DM. Mercury in the urine of children with acrodynia. Lancet 1948;1:829-30. 6. Farquhar ttG. Mercurial poisoning in early childhood. Lancet 1953;2:1186-7. 7. Cheek DB, Bandy RK, Johnson LR. The effect of mercurous chloride (calomel) and epinephrine (sympathetic stimulation) on rats: the importance of the findings to mechanisms in infantile acrodynia (pink disease). Pediatrics 1959;23:302-13.